Hospital and Neurodevelopmental Outcomes in Nano-Preterm Infants Receiving Invasive vs Noninvasive Ventilation at Birth.

Importance: Infants with gestational age between 22 0/7 and 23 6/7 weeks (referred to as nano-preterm infants) are at very high risk of adverse outcomes. Noninvasive respiratory support at birth improves outcomes in infants born at 24 0/7 to 27 6/7 weeks' gestational age. Evidence is limited on whether similar benefits of non-invasive respiratory support at birth extend to nano-preterm infants. Objective: To evaluate the hypothesis that intubation at 10 minutes or earlier after birth is associated with a higher incidence of bronchopulmonary dysplasia (BPD) or death by 36 weeks' postmenstrual age (PMA) in nano-preterm infants. Design, Setting, and Participants: This observational cohort study included all nano-preterm infants at a level IV neonatal intensive care unit who were delivered from January 1, 2014, to June 30, 2021. Infants receiving palliative or comfort care at birth were excluded. Exposures: Infants were grouped based on first intubation attempt timing after birth (>10 minutes after birth and ≤10 minutes as noninvasive and invasive respiratory support at birth groups, respectively). Main Outcomes and Measures: The primary outcome was the composite outcome of BPD (physiological definition) or death by 36 weeks' PMA. Results: All 230 consecutively born, eligible nano-preterm infants were included, of whom 88 (median [IQR] gestational age, 23.6 [23.4-23.7] weeks; 45 [51.1%] female; 54 [62.1%] Black) were in the noninvasive respiratory support at birth group and 142 (median [IQR] gestational age, 23.0 [22.4-23.3] weeks; 71 [50.0%] female; 94 [66.2%] Black) were in the invasive respiratory support at birth group. The incidence of BPD or death by 36 weeks' PMA did not differ between the noninvasive and invasive respiratory support groups (83 of 88 [94.3%] in the noninvasive group vs 129 of 142 [90.9%] in the invasive group; adjusted odds ratio, 2.09; 95% CI, 0.60-7.25; P = .24). Severe intraventricular hemorrhage or death by 36 weeks' PMA was lower in the invasive respiratory support at birth group (adjusted odds ratio, 2.20; 95% CI, 1.07-4.51; P = .03). Conclusions and Relevance: This cohort study's findings suggest that noninvasive respiratory support in the first 10 minutes after birth is feasible but is not associated with a decrease in the risk of BPD or death compared with intubation and early surfactant delivery in nano-preterm infants.

Uterine myomas: effect of prior myomectomy on pregnancy outcomes.

OBJECTIVE: Reproductive aged women with fibroids must weigh the risks and benefits of preconception myomectomy. Women with fibroids may have higher rates of fetal growth restriction (FGR) and stillbirth; however, there is a paucity of data on the impact of myomectomy on pregnancy outcomes. We compared perinatal outcomes in women with prior myomectomy versus those with no prior myomectomy and at least one fibroid ≥ 5 cm. METHODS: Retrospective cohort study of women at a single center who delivered between 2008 and 2017 with a viable intrauterine pregnancy at initial ultrasound scan and either prior myomectomy, or, in the no-myomectomy cohort, at least one fibroid ≥ 5 cm on a prenatal scan performed at < 21 weeks' gestation (wga). Pregnancies complicated by major congenital anomalies were excluded. Primary outcome was preterm birth (PTB) < 37wga. Secondary outcomes included rates of spontaneous loss, cesarean delivery (CD), abnormal placentation, malpresentation, FGR, birthweight, birthweight percentile, estimated blood loss (EBL), blood transfusion, and neonatal survival to discharge. RESULTS: A total of 290 women met inclusion criteria: 70 had a prior myomectomy, 220 women had ≥1 fibroid ≥5cm. Women with prior myomectomy were older, more likely to have private insurance, and more likely used artificial reproductive technology to conceive; 20% with prior myomectomy still had at least one ≥ 5 cm myoma on their obstetric scan. Rates of spontaneous loss were lower in the prior myomectomy group (1.4% vs 7.3%; p = .08). Of the 273 pregnancies continuing beyond 20 weeks, women with prior myomectomy had significantly more PTBs (35% vs. 21%, p = .02) and significantly different primary birth indications (p < .0001). However, after controlling for late preterm, prelabor cesareans recommended by providers in the myomectomy cohort, the difference in PTB rates was not significant (p = .13). The myomectomy group had more CDs (88% vs. 53%, p < .0001), higher EBL (1250 mL vs. 811 mL, p = .04), and a trend toward more blood transfusions (16% vs 8%, p = .05). Other selected outcomes were similar, including rates of FGR. CONCLUSIONS: Women with prior myomectomy had significantly more PTBs, due in part to more preterm, prelabor cesareans in the late preterm period. Otherwise, prior myomectomy did not confer appreciable obstetric or perinatal benefits, as patients had more CDs, and higher EBL. Recommendations to perform preterm prelabor cesareans in this population may explain some of the PTB disparity. The effect of prior myomectomy on early pregnancy loss and infertility requires further study.

cGMP Signaling Increases Antioxidant Gene Expression by Activating Forkhead Box O3A in the Colon Epithelium.

Signaling through cGMP has therapeutic potential in the colon, where it has been implicated in the suppression of colitis and colon cancer. In this study, we tested the ability of cGMP and type 2 cGMP-dependent protein kinase (PKG2) to activate forkhead box O (FoxO) in colon cancer cells and in the colon epithelium of mice. We show that activation of PKG2 in colon cancer cells inhibited cell proliferation, inhibited AKT, and activated FoxO. Treatment of colon explants with 8Br-cGMP also activated FoxO target gene expression at both RNA and protein levels, and reduced epithelial reduction-oxidation (redox) stress. FoxO3a was the most prominent isoform in the distal colon epithelium, with prominent luminal staining. FoxO3a levels were reduced in Prkg2-/- animals, and FoxO target genes were unaffected by 8Br-cGMP challenge in vitro. Treatment of mice with the phosphodiesterase-5 inhibitor vardenafil (Levitra) mobilized FoxO3a to the nucleus of luminal epithelial cells, which corresponded to increased FoxO target gene expression, reduced redox stress, and increased epithelial barrier integrity. Treatment of human colonic biopsy specimens with 8Br-cGMP also activated catalase and manganese superoxide dismutase expression, indicating that this pathway is conserved in humans. Taken together, these results identify a novel signaling pathway in the colon epithelium, where FoxO tumor suppressors could provide protection from redox stress. Moreover, this pathway is regulated by endogenous cGMP/PKG2 signaling, and can be targeted using phosphodiesterase-5 inhibitors.